NeuroVoices: Tanya Simuni, MD, FAAN, on Emerging Directions in Disease-Modifying Therapy Trials for Parkinson Disease | NeurologyLive – Clinical Neurology News and Neurology Expert Insights

Developing treatments that modify disease progression seems to remain a priority in clinical research for Parkinson disease (PD), a common neurodegenerative disorder affecting patients worldwide. Over the past couple of decades, multiple mechanisms of action have been investigated, and efforts have focused on identifying biomarkers and stratifying patients based on their clinical features, genetic background, or biologically defined subtypes. Although no therapy has confirmed disease-modifying effects, trials targeting GBA and α-synuclein and recent studies of glucagon-like peptide 1 (GLP-1) receptor agonists may provide new insights into PD progression.¹

Movement disorder expert Tanya Simuni, MD, FAAN, a professor of neurology at Northwestern University Feinberg School of Medicine, reviewed recent and ongoing disease-modifying PD trials in a plenary session presented at the 2025 International Congress of Parkinson’s Disease and Movement Disorders (MDS), held October 5-9, in Honolulu, Hawaii.² Additional topics discussed by PD experts throughout the session included challenges in patient selection and trial design. Collectively, the presentations featured during the session provided an in-depth overview of recent and ongoing efforts to develop therapies aimed at modifying the course of PD.

In a new iteration of NeuroVoices, Simuni outlined the most notable disease-modification trials recently read out in PD, emphasizing the increasing sophistication of trial design and mechanistic targeting. She highlighted 3 major areas of interest which included synuclein-targeting therapies progressing toward phase 3 evaluation, GLP-1 and dual incretin agents gaining traction, and ongoing work in genetically targeted therapeutics. In the discussion, Simuni noted that advances in biologic characterization, participant selection, and target-engagement tools may be bringing the field closer to meaningful disease modification than ever before.

NeurologyLive: For readers who missed your plenary session, can you briefly summarize the major themes you highlighted on recent and ongoing clinical trials in Parkinson disease and the key studies you chose to focus on?

Tatyana Simuni, MD: I presented in the plenary session on past, present, and future clinical trials, and I specifically focused on disease-modification trials recently completed. First of all, the landscape is tremendously active. There is no way that I could cover even a fraction of the studies going on across the continuum from the early development to the later phases. I’ve chosen to focus on the studies that have read out in the last year and consistent with that, there are 3 themes.

The theme of synuclein-targeting therapies—two phase 2 studies read out; the theme of GLP-1 is extremely hot—the role of these agents, GLP-1s and dual incretins, in disease modification specifically in PD and across neurodegeneration. I covered that topic. There was a study of a tyrosine kinase C-Abl inhibitor; again, that is not a new story, but a new drug with much better pharmacological characteristics and safety profile compared with the nilotinib study that brought a tremendous amount of attention about, by now, 6 years ago. I covered that. I briefly covered an essentially important topic of genetically targeted therapeutics. The reason I covered that briefly is not because of reduced importance, but because none of the studies have read out in the last year, and there was a separate session focused on translational genetically targeted therapeutics.

What stands out to you about these disease-modifying drugs and what should clinicians be taking away from some of the data that has read out in the last year?

Disease modification, as of today, is an essential need and an unmet goal. We’ve been trying for 30-plus years, and not a single study has had definitively positive results. In regards to where we stand today, I believe that we are truly on the precipice of a major inflection point. Why am I saying that? I’m a clinical trialist, and the focus of my career is development and implementation of clinical trials. But aside from me being an involved entity, I believe we have better tools.

We have better tools to identify the right participants, to biologically define those individuals. We have better drugs that have been developed targeting specific mechanisms. Although we still have challenges in how to prove that the drug truly targeted the mechanism in an individual—we’re talking about the readouts of target engagement, all those technical terms that allow us to definitively test the hypothesis—we still have better tools than we did before. It’s the right person, right drug, right biological target. If we solve that triangle, we’ll get there.

Are there any specific approaches among these therapies being investigated that you find particularly exciting, whether it’s the disease target, the mechanism of action of the therapy, or how it’s delivered?

In regard to which are the front-runners or which are at the top of the hierarchy of importance, I don’t think that we should prioritize that way. There are multiple different mechanistic targets. But from the standpoint of front-running, synuclein-targeting therapies make biological sense. They have been in development for now 6 or 7-plus years. Again, we don’t have a success story, but we have the first drug going into phase 3 development. That is the Roche prasinezumab synuclein-targeting monoclonal antibody.

They’re going into phase 3 based on the readout of their phase 2 study—part A—that they have publicly presented. It hasn’t been published yet; it was presented in the guided poster tour at this meeting as well. They missed their primary end point, but they had enough evidence in the prespecified secondary end points that led them to make the decision to proceed with the phase 3 study. Whether the phase 3 study will be positive, the data will show. But whether the field will learn a tremendous amount from that study, I will make no other comment.

Transcript edited for clarity. Click here for more coverage of MDS 2025.

REFERENCES
1. Fabbri M, Corvol JC, Rascol O. Disease-Modifying Therapies in Parkinson’s Disease. Neurol Clin. 2025;43(2):319-340. doi:10.1016/j.ncl.2024.12.009
2. Simuni T. Recent and Ongoing Trials. Presented at: 2025 MDS Congress; October 5-9; Honolulu, Hawaii. Disease-Modifying Trials for Parkinson’s Disease: Past, Present, and Future.

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